New biomarkers linked to early diagnosis of breast cancer

Measuring the amount of certain protein fragments and microRNAs in a woman’s blood and breast tissue might enable the early diagnosis of breast cancer or prediction of its metastasis, respectively, according to two new published studies.

Cancer is the second leading cause of death in both men and women in the United States. However, women have a higher chance than men of being diagnosed with cancer before age 60 years due to breast cancer development. Metastases in the later stages of breast cancer cause the majority of deaths associated with the disease, making early detection crucial to patient survival.

Testing for the right biomarkers—biological molecules whose presence indicates a disease—could increase survival rates more than current screening methods such as mammography. Until recently, however, scientists have discovered disappointingly few useful cancer markers. Two studies published in Clinical Chemistry (2014; 60(1):233-242 and 197-205) discuss promising new biomarkers.

A team of researchers led by Ye Hu, PhD, of Weill Cornell Medical College of Cornell University, New York, New York, has discovered several promising new biomarkers that could revolutionize the way breast cancer is diagnosed. In their article, the researchers show that levels of the enzyme carboxypeptidase N (CPN) are higher in breast cancer tissue than in healthy tissues. This enzyme produces six protein fragments, or peptides, that then enter the bloodstream. Hu’s team found that a rise in blood concentrations of these six peptides strongly correlates with increases of CPN, which in turn indicates the presence of breast cancer.

“Our results represent a first demonstration, to our knowledge, that clearly links the proteolytic activity of CPN, particularly at tumor sites, to the cleavage patterns of its catalytic substrates in the blood,” said Hu. “These biomarkers show strong potential for the noninvasive and early diagnosis of breast cancer. We advocate their use … certainly to be detected and identified before metastasis, and perhaps even before the tumor presents with any observable characteristics commonly used in the clinic.”

Another research team headed by Evi Lianidou, PhD, of the University of Athens in Greece, set out to address the current inability to predict at the time of breast cancer diagnosis whether a patient will experience a relapse or metastasis. Many recent studies have shown that microRNAs (miRNAs), a type of molecule that turns genes on and off, can play a critical role in the metastasis process. Upon examining this further, Lianidou’s team found that breast cancer patients who experienced quick relapses tended to have high and low levels of the microRNAs miR-21 and miR-205, respectively, in their tumor tissue. The team also discovered a connection between low levels of miR-205 and reduced overall survival.

Testing for these miRNAs or CPN-catalyzed peptides in early or potential breast cancer patients could ensure that women at risk of metastasis receive life-saving preventive treatment.